Ondansetron

Ondansetron

Trade names	Zofran
Clinical data
Drug class	Anti-emetic
Uses	Prevention and treatment of chemo-induced, radiation induced nausea and vomiting, prevention of postoperative nausea and vomiting
Contraindications	Prolonged QT intervals, patients taking apomorphine
Routes of administration	PO, IM, IV
Dosage
Pharmacodynamics
Mechanism of action	5HT3 antagonist
Adverse effects	cardiac arrhythmias, cardiac arrest, constipation, headaches
Pharmacokinetics
Metabolism	Liver oxidation followed by glucuronidation and sulfate conjugation
Elimination half-life	4 hours
Physical and chemical data
Article quality
Editor rating	Comprehensive
User likes	0

Ondansetron is a 5HT₃ receptor antagonist that is commonly used for the treatment and prophylaxis of chemo induced nausea and vomiting, radiation induced nausea and vomiting, and postoperative nausea and vomiting.

Uses

• treatment and prevention of chemo-induced nausea and vomiting
• treatment and prevention of radiation induced nausea and vomiting
• Prevention of postoperative nausea and vomiting
• off-label use for the prevention of nausea and vomiting associated with pregnancy

Contraindications

Absolute contraindications

• Prolonged QT intervals
• Patients taking apomorphine as it can cause hypotension and loss of consciousness

Precautions

• Maximum dose of 16 mg IV due to risk of QT prolongation and arrhythmias
• Maximum dose decreased to 8 mg IV or 8 mg PO in severe hepatic impairment
• Dissolving tablets formulations contain phenylalanine which can lead to irreversible neurological damage in phenylketonuria (PKU)

Pharmacology

Pharmacodynamics

• Metabolized by CYP2D6, CYP3A4, CYP2E1, CYP1A2 initially with oxidation followed by glucuronide and sulfate conjugations
  • Many polymorphisms with four different phenotypes
    • Poor metabolizer (no functional allele)
    • Intermediate metabolizer (less activity than one functional allele)
    • Extensive metabolizer (two functional allele, most common phenotype)
    • Ultrarapid metabolizer (three functional allele)

Mechanism of action

• Antagonism of the 5HT₃ receptors
• Centrally, ondansetron antagonizes the 5HT₃ receptors in the area postrema
• Peripherally, ondansetron antagonizes the 5HT₃ receptors on the vagus nerve within the GI tracts which forms synapses within the nucleus tracts solitarius (a region also responsible for vomiting)
  • Predominant mechanism for its anti-emetic effect

Adverse effects

• Cardiac arrhythmia
• Cardiac arrest
• Constipation
• Headache
• dry mouth
• malaise
• drowsiness
• sedation
• pruritus
• transient elevation in liver function test

Pharmacokinetics

• Peak plasma concentration about 1.5 hours after an 8 mg PO dose

• Plasma half life is approximately 4 hours

Chemistry and formulation

Available in PO, intramuscular (IM), and intravenous (IV).

References

Zabirowicz, Eric S.; Gan, Tong J. (2019), "Pharmacology of Postoperative Nausea and Vomiting", Pharmacology and Physiology for Anesthesia, Elsevier, pp. 671–692, retrieved 2023-01-05

Griddine, Alexandria; Bush, Jeffrey S. (2022), "Ondansetron", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29763014, retrieved 2023-01-05